Development of appropriate animal models of glaucoma is a critical step for understanding the molecular mechanisms of this blinding disease. We develop mouse and rat mouse models of glaucoma using a transgenic approach. It is now well established that mutations in the myocilin gene may lead to juvenile open-angle glaucoma and, in some cases, to adult onset glaucoma. We continued our previous studies on the characterization of a transgenic mouse line containing BAC (bacterial artificial chromosome) with a point mutation (Tyr437His) in the human myocilin gene. This line demonstrated a moderate elevation of intraocular pressure, a 20-25% decrease in the amount of retinal ganglion cells in the peripheral retina of one year old transgenic mice compared to control animals, and partial inhibition of myocilin secretion into the aqueous humor. These pathological changes were similar to those previously observed in a transgenic mouse line containing BAC with a point mutation (Tyr423His) in the mouse myocilin gene. Several transgenic rat lines expressing mutated human or mouse myocilin were produced and are under investigation. Transgenic mice and rats expressing mutated mouse and human myocilin may represent a very useful genetic model of glaucoma.[unreadable] [unreadable] We continue to study properties of two other proteins, olfactomedin 1 and optimedin, which are similar to myocilin and contain the olfactomedin domain. Both of these genes are expressed in the mammalian retina. We demonstrated that aggregation of differentiating optimedin-expressing PC12 cells in the presence of nerve growth factor is due to increased level of N-cadherin. Although optimedin and olfactomedin 1 are 66% identical, expression of olfactomedin in NGF-stimulated PC12 cells induced neurite formation which was inhibited in optimedin-expressing cells. Olfactomedin did not induce N-cadherin expression but instead activated expression of neurofilament protein NF160.